Malignant mouse plasma cells (myelomas) producing paraproteins with the ability to bind specific antigen have been adapted to continuous growth in tissue culture. These cells can be cloned at high efficiency in soft agar using fibroblast feeder layers. Variant clones will be isolated which have lost the ability to synthesize one of the three polypeptide chains, produce chains with altered primary structure, no longer bind antigen, assemble their immunoglobulin at a different rate or via an altered pathway, or process their immunoglobulin in a different manner. These variants will be characterized with respect to the frequency with which they occur and with respect to the type of change involved. Characterization will be done using SDS polyacrylamide gels, isoelectric focusing gels, and peptide mapping. Radioimmunoassays will be established to assay alterations in antigen binding. Complementation studies will be attempted using somatic cell hybridization. Isolation and characterization of these variants should give information about the structure-function relationships within the immunoglobulin molecule, the genetic organization of the immunoglobulin locus, and the cellular functions in immunoglobulin biosynthesis.